Glomerulonephritis is a major cause of morbidity and death in young people. Chronic dialysis as a result of GN consumes a significant proportion of the gross national product of the United States. Our capacity to control the relentless progress of GN is limited, partly because of poor understanding of the pathogenesis of GN. The Hageman factor (HF) system is potentially a powerful initiator of several inflammatory pathways including coagulation, fibrinolysis, kinin and angiotensin formation, and chemotaxis. There is considerable circumstantial evidence (both from studies using isolated glomerular basement membrane and from the observation that some individuals with GN have low plasma HF levels) that the HF system could be activated in GN. The purpose of this study is to test this hypothesis using a) recently acquired understanding of the biochemical events occurring during activation of the HF system, and b) purified proteins of the HF system from human and rabbit plasma. These proteins can be radiolabeled and followed during the experimental nephritic process. In particular, information can be obtained about proportions of molecules undergoing activation, number of molecules localized in the kidney and rates of turnover of molecules. These powerful probes will enable us to assess the contribution of the HF system to GN in a rabbit model of GN. If this contribution appears significant a rational therapeutic approach could be designed to interfere with HF system activation.